Department of Biological and Biomedical Sciences, North Carolina Central University, Durham, North Carolina, USA.
Integrated Biosciences (INBS) Doctoral Program, North Carolina Central University, Durham, North Carolina, USA.
J Med Virol. 2024 Oct;96(10):e29958. doi: 10.1002/jmv.29958.
Kaposi's Sarcoma Herpesvirus (KSHV) is the causative agent of several human diseases. There are no cures for KSHV infection. KSHV establishes biphasic lifelong infections. During the lytic phase, new genomes are replicated by seven viral DNA replication proteins. The processivity factor's (PF-8) functions to tether DNA polymerase to DNA, so new viral genomes are efficiently synthesized. PF-8 self-associates, interacts with KSHV DNA replication proteins and the viral DNA. Inhibition of viral DNA replication would diminish the infection within a host and reduce transmission to new individuals. In this review we summarize PF-8 molecular and structural studies, detail the essential protein-protein and nucleic acid interactions needed for efficient lytic DNA replication, identify future areas for investigation and propose PF-8 as a promising antiviral target. Additionally, we discuss similarities that the processivity factor from Epstein-Barr virus shares with PF-8, which could promote a pan-herpesvirus antiviral therapeutic targeting strategy.
卡波济肉瘤相关疱疹病毒（KSHV）是几种人类疾病的致病因子。目前尚无治疗 KSHV 感染的方法。KSHV 建立了双相终身感染。在裂解期，新的基因组由七种病毒 DNA 复制蛋白复制。过程因子（PF-8）的功能是将 DNA 聚合酶与 DNA 连接，从而有效地合成新的病毒基因组。PF-8 自身缔合，与 KSHV DNA 复制蛋白和病毒 DNA 相互作用。抑制病毒 DNA 复制将减少宿主内的感染并减少向新个体的传播。在这篇综述中，我们总结了 PF-8 的分子和结构研究，详细描述了有效裂解 DNA 复制所需的必需蛋白-蛋白和核酸相互作用，确定了未来的研究领域，并提出 PF-8 作为有前途的抗病毒靶标。此外，我们还讨论了 Epstein-Barr 病毒的过程因子与 PF-8 之间的相似之处，这可能会促进一种针对泛疱疹病毒的抗病毒治疗靶向策略。
